uNreveal the rOle of SpaRtin in MitochondriA

Objective

Troyer Syndrome (TS) is a rare and complex variant of Hereditary Spastic Paraplegia (HSP), driven by mutations in the SPG20 gene, which encodes the Spartin protein (SPART). This syndrome, characterized by neurodevelopmental impairments, remains poorly understood, particularly regarding the impact of SPART mutations on mitochondrial function. Although genomic technologies like Whole Exome and Whole Genome Sequencing have advanced our knowledge, the link between SPART mutations and metabolic dysfunctions in TS is still unclear. This project aims to fill this gap by integrating transcriptomics and metabolomics to study the effects of SPART mutations across three cellular models: fibroblasts derived from TS patients, motor neurons differentiated from patient-derived iPSCs, and CRISPR-Cas9-edited cells carrying specific SPART mutations. The hypothesis is that SPART mutations disrupt mitochondrial metabolic processes, which are central to TS pathogenesis. By employing these advanced -omics and functional approaches, we will map the metabolic alterations, aiming to correct these dysfunctions through targeted metabolite supplementation. This research not only offers a novel perspective on the molecular mechanisms underlying TS but also paves the way for potential therapeutic interventions. The project will significantly enhance my expertise in cutting-edge biomedical research while contributing valuable insights to the field of neurodegenerative diseases, potentially leading to improved diagnostics and therapies for TS and related disorders.